Cetirizine is an antiallergic compound of the formula: ##STR1## the chemical name of which is [2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl-]ethoxy]acetic acid.
Cetirizine is well known to have an antiallergic effect, for example, by oral administration, and it is particularly useful as an antiallergic agent with significant specificity to histamine (see, e.g., JP-B 63-11353).
In ophthalmic or nasal allergic diseases, taking the former as an example, systemic symptoms are frequently associated with ophthalmic symptoms, in which case the oral administration of an antiallergic agent is effective for their treatment. There are, however, some cases where no systemic abnormality can be detected even if marked changes are found in the eyes, and in particular, lesions found only in the eyes are not always accompanied by systemic abnormality. In such cases, topical therapy is preferred to systemic therapy because of its safety and effectiveness. This relationship between the systemic and topical symptoms holds true even in the field of otorhinology.
As an ophthalmic solution containing cetirizine, there is disclosed an antiallergic and antihistaminic composition (see, e.g., JP-A 4-9339). This composition comprises an antiallergic agent and an antihistaminic agent capable of exhibiting effective antihistaminic action when used in combination with the antiallergic agent. Cetirizine is exemplified as such an antihistaminic agent that is one of the essential ingredients of the composition.
However, no report has hitherto been made of an effect attained by the ophthalmic application of an antiallergic composition containing cetirizine as only one active ingredient.
Cetirizine has, although it is readily soluble in water, a disadvantage that a solution of cetirizine at low concentrations (below 1 w/v %) may cause the deposition of insoluble matter with the lapse of time, thereby decreasing the stability as an aqueous solution. This seems to be because cetirizine is one of the diphenylmethane derivatives capable of forming molecular aggregates (see, e.g., Masayuki Nakagaki (ed.), "Bussei-Butsuri (Material Science)," Nankodo, Tokyo, 1986, pp. 238-239). On the other hand, a solution of cetirizine at high concentrations where no insoluble matter will be deposited has strong irritating properties when applied in ophthalmic or nasal use, and it cannot be used as an ophthalmic or nasal solution. For this reason, there has not yet been developed an antiallergic composition for practical use containing cetirizine as the main active ingredient, which can be applied as an ophthalmic or nasal solution.
In general, it is difficult in most cases to prepare an ophthalmic or nasal solution with satisfactory safety and stability from a drug having irritating properties or capable of forming molecular aggregates, although it depends on the kind of the drug used.
Cyclodextrin compounds are well known to have a property of taking various drugs into their central portion to form clathrate compounds of these drugs because they are cyclic sugars. Therefore, cyclodextrin compounds have hitherto been used for the purpose of making a solution of various slightly-soluble drugs or improving the stability of drugs. However, when a cyclodextrin compound is blended with a certain drug, it becomes difficult in most cases to exhibit the efficacy of the drug, and this problem is particularly serious for external preparations.